Changes in body temperature and circulating levels of interleukin-6 after intra-arterial injections or infusions of tumor necrosis factor α in guinea pigs

Tumor necrosis factor (TNF) is released systematically during the early phase of endotoxin induced fever. To study the effects of this cytokine in guinea pigs, 2 g TNF were intra-arterially injected as a bolus or slowly infused within 60 min. Both modes of administration induced a biphasic elevation of the animals' abdominal temperature lasting 6 h and stimulated the release of endogenous interleukin-6 (IL-6)-like activity. The second phase of the thermal response and the release of endogenous IL-6-like activity were significantly higher, when TNF was slowly infused into the animals' circulation, in spite of a transiently higher TNF-like activity after the bolus injection of TNF. Both TNF and IL-6 may therefore be regarded as candidates to trigger the febrile response in guinea pigs.     

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.     

Essentially narrative explanations

This essay argues that narrative explanations prove uniquely suited to answering certain explanatory questions, and offers reasons why recognizing a type of statement that requires narrative explanations crucially informs on their assessment. My explication of narrative explanation begins by identifying two interrelated sources of philosophical unhappiness with them. The first I term the problem of logical formlessness and the second the problem of evaluative intractability. With regard to the first, narratives simply do not appear to instantiate any logical form recognized as inference licensing. But absent a means of identifying inferential links, what justifies connecting explanans and explanandum? Evaluative intractability, the second problem, thus seems a direct consequence. This essay shows exactly why these complaints prove unfounded by explicating narrative explanations in the process of answering three interrelated questions. First, what determines that an explanation has in some critical or essential respect a narrative form? Second, how does a narrative in such cases come to constitute a plausible explanation? Third, how do the first two considerations yield a basis for evaluating an explanation offered as a narrative? Answers to each of these questions include illustrations of actual narrative explanations and also function to underline attendant dimensions of evaluation.     

Will the real scientists please stand up? dead ends and live issues in the explanation of scientific knowledge

Reflection on the method of science has become increasingly thinner since Kant. If there's any upshot of that part of modern philosophy, it's that the scientists didn't have a secret. There isn't something there that's either effable or ineffable. To understand how they do what they do is pretty much like understanding how any other bunch of skilled craftsmen do what they do. Kuhn's reduction of philosophy of science to sociology of science doesn't point to an ineffable secret of success; it leaves us without the notion of the secret of success.Relativism is the view that every belief on a certain topic, or perhaps, about any topic, is as good as every other. No one holds this view. Except for the occasional co-operative freshman, one cannot find anybody who says that two incompatible opinions on an important topic are equally good. The philosophers who get called ‘relativists’ are those who say that the grounds for choosing between such opinions are less algorithmic than had been thought.Richard Rorty1,2     

Rapid effects of insulin on cyclic GMP location in an intact protozoan.

We studied rapid changes in location of cyclic GMP in Tetrahymena pyriformis. Insulin caused cGMP localization in cilia and near the plasma membrane (0.5-1 min). Later (1-5 min) cGMP localization was diffuse in cytoplasm with perinuclear accentuation. Inactive insulin analogs did not elicit these changes.     

Cell-free synthesis and processing of multiple precursors to glucagon

Glucagon, a polypeptide hormone of 29 amino acids, is synthesized in the islets of Langerhans and immunoreactive forms of the molecule have been found in several tissues. Like many other polypeptide hormones, glucagon is synthesized via a larger precursor molecular, proglucagon; however, estimates of its size vary considerably and the biosynthetic relationship between some of the putative precursors and authentic secreted glucagon is unclear. Consequently it was of interest to investigate the primary translation product of glucagon mRNA to relate its size to that of previously described glucagon precursors. Here we provide evidence for three distinct immunoreactive preproglucagon molecules, two of which have an apparent molecular weight (MW) of approximately 16,000 (16K). Furthermore, when microsomal membranes were present during translation, the nascent 14K preproglucagon polypeptides were processed to proglucagon with a higher apparent MW of 15,000. In contrast, the nascent 16K preproglucagon was co-translationally processed to a slightly smaller polypeptide. The data indicate that the 14K and 16K preproglucagons undergo different types of post-translational modification.     

Converting enzyme content of different tissues of the rat

Résumé On a dosé l'enzyme de conversion dans différents tissus du rat au moyen d'une méthode chimique mesurant la libération d'histidyl-leucine à partir du substrat synthétique Z-phe-his-leu. Le poumon contient au moins 8 fois plus d'enzyme que tous les autres tissus étudiés. Il en contient notamment plus de 100 fois plus que le foie.